A Phase I Study of Individual Adult and Pediatric Patient Dose-escalated Interleukin-2 Therapy for Refractory Chronic Graft-versus-Host-Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of 8-week Individual patient dose-escalated Interleukin-2
研究概览
简要总结
This research study is a way of gaining new knowledge about the treatment for cGVHD that has not responded to steroids. This research study is evaluating a drug called Interleukin-2 (IL-2) as a possible treatment for cGVHD. In this Phase I study, the investigators are looking to see if 8- week individual patient dose- escalated IL-2 therapy for cGVHD is safe and its effects on your immune cells.
详细描述
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved IL-2 for the treatment of cGVHD but it has been approved for metastatic renal cell carcinoma (MCC), and metastatic melanoma.
Chronic GVHD is a medical condition that may occur after the participant has received bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the participant's body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host-disease. Traditional standard therapy to treat cGVHD is prednisone (steroids). Interleukin-2 (IL-2) is a natural protein involved with regulation of white blood cells (WBCs). WBCs are part of the immune system.The investigators looking to see whether IL-2 helps control chronic GVHD by stopping the donor's immune system from 'rejecting' the participant's body.
This study will look to see if increasing the dose level of study drug every two weeks can be administered safely without severe or unmanageable side effects in participants that have cGVHD. Depending on how well you tolerate your initial dose level and subsequent dose levels, your study drug dose level may be increased a maximum of two times. These increases in dose levels will occur two weeks apart. All participants on the study will start at the same dose level.
Study Drug: You will administer, or have someone else administer if you are unable to yourself, IL-2 through an injection under your skin. You should rotate the injection site, if possible. You will do this once every day for 8- weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Participants with ongoing prednisone (equivalent) dose requirement > 1 mg/kg/day (or equivalent).
- •Participants with concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).
- •Participants with new immunosuppressive medication, extra-corporeal photopheresis or rituximab therapy initiated in the 4 weeks prior.
- •Participant with post-transplant exposure to donor lymphocyte infusion (DLI), or T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior.
- •Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the Principal Investigator. Previous fixed-dose IL-2 therapy that was discontinued prior to 4 weeks is permitted.
- •Participants with active malignant relapse or recrudescence of their prior hematologic disorder.
- •Participants with inability to comply with IL-2 treatment regimen.
- •Organ transplant (allograft) recipient.
- •HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used after allogeneic HSCT. In addition, these individuals are at increased risk of lethal infections. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- •History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to IL-
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after HSCT.
- •Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued.
研究组 & 干预措施
Interleukin-2 (IL-2)
Interleukin-2: Each participant will receive daily subcutaneous IL-2 for self-administration per cycle. Each participant will start at Dose Level A. In the abscence of DLTs or severe non-DLT adverse events, participants will have daily SC IL-2 dose-escalated at Week 2 (to dose level B) and at Week 4 (to Dose Level C), and continue on their maximum tolerated dose (MTD) IL-2 for 4 weeks total.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of 8-week Individual patient dose-escalated Interleukin-2
时间窗: 8 weeks
Participants will be evaluated over the course of the 8-week treatment for Dose-Limiting Toxicities (DLTs) from the individual dose-escalated IL-2
次要结局
- Malignant Relapse Rate(1 Year)
- Overall cGVHD Clinical Response Rate(Baseline, 8 Weeks)
- Overall Survival Rate(1 year)
研究者
John Koreth, MD
Principal Investigator
Dana-Farber Cancer Institute